Patient sensory response evaluation for neuromodulation efficacy rating

ABSTRACT

The invention is directed to a technique for rating neuromodulation efficacy based on evaluation of the response of the patient to sensory stimuli with and without delivery of neuromodulation therapy. In addition, the invention may provide a system capable of delivering sensory stimuli on a quantitative basis in a coordinated manner with delivery of neuromodulation therapy. A device programmer may provide a platform for controlling delivery of the sensory stimuli, delivery of neuromodulation therapy, and generation of rating information for neuromodulation efficacy based on patient sensory response to the stimuli. In operation, the programmer controls application of selected sensory stimuli to the patient&#39;s body and records the patient&#39;s verbal or physiological responses to the stimuli. This invention can be used to be a diagnostic or prognostic test that a given neuromodulation therapy, such as neurostimulation or drug delivery, is and will be successful.

This application claims the benefit of U.S. provisional application No.60/508,318, filed Oct. 2, 2003, and U.S. provisional application No.60/508,354, filed Oct. 3, 2003, the entire content of each of which isincorporated herein by reference.

TECHNICAL FIELD

The invention relates to neuromodulation therapy and, more particularly,to techniques for determining and rating neuromodulation efficacy to aidin selection of neuromodulation programs.

BACKGROUND

Implantable medical devices are used to deliver neuromodulation therapyto patients to treat a variety of symptoms or conditions such as chronicpain, tremor, Parkinson's disease, epilepsy, incontinence, orgastroparesis. Neuromodulation may involve delivery of neurostimulationtherapy, in the form of electrical pulses, via one or more leads thatinclude electrodes located proximate to the brain, spinal cord,peripheral nerves, skin, neuronal ganglia, or nerves to organs.Neuromodulation may also involve use of an implantable drug deliverydevice, to chronically deliver metered dosages of a drug to targetregions in the body via a catheter. Neuromodulation may involve thesimultaneous use of both modalities, i.e., neurostimulation and drugdelivery, for optimal efficacy.

Prior to implantation of a neuromodulation device, the patient mayengage in a trial neuromodulation period, in which the patient receivesan implanted or external trial neuromodulation device on a temporarybasis. An external trial neurostimulator screener, for example, may becoupled to an implanted lead via a percutaneous lead extension. Ineither case, the trial neuromodulation permits a clinician to observeneuromodulation efficacy and determine whether implantation of a chronicneuromodulation device is advisable.

The trial neuromodulation period also may assist the clinician inselecting values for a number of programmable parameters in order todefine the neuromodulation therapy to be delivered to a patient. Forexample, for a neurostimulation, the clinician may select an amplitude,which may be current- or voltage-controlled, and pulse width for astimulation waveform to be delivered to the patient, as well as a rateat which the pulses are to be delivered to the patient. In addition, theclinician also selects particular electrodes within an electrode set ona lead to be used to deliver the pulses, and the polarities of theselected electrodes. With drug delivery, the clinician may select dosingand concentration of the drug in the device, and timing intervals also.

The results of the trial neuromodulation process can be inconsistent.For example, the trial neuromodulation process may be hampered bysubjective and possibly inconsistent feedback from the patientconcerning observed efficacy. In addition, the trial neuromodulationprocess may yield information that is indicative of short-term,diagnostic efficacy, but less indicative of long-term, prognosticsuccess.

SUMMARY

In general, the invention is directed to techniques for determining andrating neuromodulation efficacy based on evaluation of the response ofthe patient to external sensory stimuli at different times. Inparticular, the patient response is evaluated before intervention bydelivery of neuromodulation therapy, such as neurostimulation, and thenduring delivery of neuromodulation therapy to detect changes in thepatient sensory response.

Evaluation of changes in patient sensory response caused byneuromodulation can provide a prediction of efficacy of neuromodulationin general, including electrical neurostimulation and drug delivery.Hence, the invention may provide a clinician with not only a diagnostictool in determining short term, clinical results obtained fromneurostimulation, but also a prognostic tool in predicting the likelyefficacy of a chronically implanted neurostimulator or chronicallyimplanted drug delivery device over a longer period of time. In otherwords, the invention may support evaluation of both diagnostic, i.e.,short term, efficacy, and prognostic, i.e., long term, efficacy.

In addition, the invention may provide a system capable of deliveringsensory stimuli on a quantitative basis in a manner coordinated withdelivery of neuromodulation therapy. A neuromodulation device programmermay provide a platform for controlling delivery of the sensory stimuli,delivery of neuromodulation therapy, and generation of useful ratinginformation about neuromodulation efficacy based on patient sensoryresponse to the stimuli. In operation, the programmer controlsapplication of selected sensory stimuli to the patient's body andrecords the patient's verbal or physiological responses to the stimuli.

The invention may support delivery of different types of sensorystimuli, e.g., electrical and vibratory stimuli, and evaluation ofneuromodulation efficacy based on patient response to the differentsensory stimuli types before and during delivery of neurostimulationtherapy. Other sensory stimuli include tactile, thermal, pressure andchemical stimuli. For example, the effect of neurostimulation therapy onsensory perception thresholds, sensory tolerance limits and the like fordifferent types of stimuli may be evaluated to determine short-termefficacy of neuromodulation. Moreover, the effect of neurostimulationtherapy on patient response to some types of sensory stimuli may beprognostic for long-term success of the neuromodulation therapy. In eachcase, consideration of the patient's responses to different types ofstimuli may provide a reliable correlation that promotes selectivity andspecificity.

In one embodiment, the invention provides a method comprising applying afirst type of external sensory stimulation to a patient, obtaining abaseline measurement of patient sensory response to the first type ofexternal sensory stimulation, applying a second type of external sensorystimulation to a patient, and obtaining a baseline measurement ofpatient sensory response to the second type of external sensorystimulation. The method further comprises applying neuromodulationtherapy to the patient simultaneously with application of the first typeof external sensory stimulation, obtaining a test measurement of patientsensory response to the first type of external sensory stimulationduring simultaneous application of the first type of external sensorystimulation and the neuromodulation therapy, applying neuromodulationtherapy to the patient simultaneously with application of the secondtype of external sensory stimulation, obtaining a test measurement ofpatient sensory response to the second type of external sensorystimulation during simultaneous application of the second type ofexternal sensory stimulation and the neuromodulation therapy, andevaluating efficacy of the neuromodulation therapy based on a comparisonof the baseline measurements and the test measurements.

In another embodiment, the invention provides a system comprising afirst sensory stimulation unit to apply a first type of external sensorystimulation to a patient, and a second sensory stimulation unit to applya second type of external sensory stimulation to the patient, aneuromodulation unit to apply neuromodulation therapy to the patient.The system further comprises a device to obtain a baseline measurementof patient sensory response to the first type of external sensorystimulation without application of the neuromodulation therapy, obtain abaseline measurement of patient sensory response to the second type ofexternal sensory stimulation without application of the neuromodulationtherapy, obtain a test measurement of patient sensory response tosimultaneous application of the first type of external sensorystimulation and the neuromodulation therapy, and obtain a testmeasurement of patient sensory response to simultaneous application ofthe second type of external sensory stimulation and the neuromodulationtherapy. The device evaluates efficacy of the neuromodulation therapybased on a comparison of the baseline measurements and the testmeasurements.

In an added embodiment, the invention provides a method comprisingapplying external sensory stimulation to a patient, wherein the externalsensory stimulation includes at least one of tactile, vibrational,thermal, pressure, chemical stimulation. The method further comprisesobtaining a baseline measurement of patient sensory response to theexternal sensory stimulation, applying neuromodulation therapy to thepatient simultaneously with application of the external sensorystimulation, obtaining a test measurement of patient sensory response tothe external sensory stimulation during simultaneous application of theexternal sensory stimulation and the neuromodulation therapy, andevaluating efficacy of the neuromodulation therapy based on a comparisonof the baseline measurements and the test measurements.

In a further embodiment, the invention provides a system comprising asensory stimulation unit to apply external sensory stimulation to apatient, wherein the external sensory stimulation includes at least oneof tactile, vibrational, thermal, pressure, chemical stimulation, and aneuromodulation unit to apply neuromodulation therapy to the patient. Adevice obtains a baseline measurement of patient sensory response to theexternal sensory stimulation without application of the neuromodulationtherapy, obtains a test measurement of patient sensory response tosimultaneous application of the external sensory stimulation and theneuromodulation therapy, and evaluates efficacy of the neuromodulationtherapy based on a comparison of the baseline measurements and the testmeasurements.

According to an added embodiment, changes in patient sensory responsemay be evaluated for a second external sensory stimulus only if thechanges in patient sensory response for a first external sensor stimulusdo not indicate a sufficiently large change, creating ambiguity. On theother hand, if the first measurements are sufficiently large, the secondmeasurements can be avoided. In particular, according to this approach,baseline vibration measurements are obtained during application of afirst type of stimulation, e.g., vibratory stimulation, to the patient.

Then, baseline measurements may be obtained for a second type ofstimulation, e.g., electrical stimulation. Upon activation of aneurostimulation program, similar “test” measurements are obtained forthe vibration, and the baseline and neurostimulation “test” vibrationmeasurements are compared. The “test” measurement refers to themeasurement obtained during simultaneous activation of theneurostimulation program, and the external sensory stimulation.

If the comparison between the baseline measurement and the testmeasurement is not favorable to the point of being definitive, thenelectrical measurements may be taken for patient sensory response toexternal electrical stimulation: If the vibratory comparison isdefinitive, however, the clinician or patient may simply forego theelectrical test measurement and conclude that the applicableneurostimulation program is not likely to be efficacious.

Baseline measurements may be done at any time either before applicationof the neuromodulation therapy, or by turning off the neuromodulationtherapy, and waiting for a sufficient period of time so that the effectsof neuromodulation therapy have substantially diminished, typicallybetween two and 48 hours.

As a variation, the process may take the baseline electrical measurementand neurostimulation test electrical measurement only if the vibratorymeasurements are equivocal, i.e., not definitive. In this case, thevibratory stimulus serves as a primary threshold test. In anotherembodiment, if a patient's visual analog scale (VAS) score rises withneuromodulation, then the process can be terminated without testingother measurements such as electrical or vibratory external sensorystimulation.

In some embodiments, the neuromodulation used in evaluating changes inpatient sensory response may be delivered by a trial neurostimulator viaan implanted lead and a percutaneous lead extension. Alternatively, thetrial neurostimulator may be an implanted neurostimulation device. Inother embodiments, however, the neurostimulation may be delivered by atranscutaneous electrical neurostimulation (TENS) device.Advantageously, the use of a TENS device would not require any surgeryor non-surgical implantations of leads. Instead, electrodes associatedwith the TENS device may be attached to the skin of the patient. As afurther alternative, neuromodulation may be delivered by application ofa drug to a patient orally, by injection, by implantable drug pump, byexternal drug pump, by transdermal patch or other delivery mechanisms.

The invention may provide a number of advantages. For example, theinvention may allow a clinician to better judge the likely efficacy ofneuromodulation therapy for a patient, on both a short-term andlong-term basis. In this manner, the clinician may be better equipped tomake decisions about whether to implant a neuromodulation device on achronic basis.

For example, the invention may be useful in diagnosing features of thepatient's physiological sensory state, and providing prognosticinformation about the long-term efficacy of neuromodulation therapy forthe patient. The result may provide greater certainty in the selectionof candidates for neuromodulation therapy, especially when patientsensory results are correlated for different types of sensory stimuli toprovide greater selectively and specificity.

The details of one or more embodiments of the invention are set forth inthe accompanying drawings and the description below. Other features,objects, and advantages of the invention will be apparent from thedescription and drawings, and from the claims.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a block diagram illustrating a system for evaluating patientsensory response to rate neuromodulation efficacy.

FIG. 2 is a flow diagram illustrating a technique for evaluating patientsensory response to rate neuromodulation efficacy.

FIG. 3 is a conceptual diagram illustrating the system of FIG. 1 ingreater detail.

FIG. 4 is a block diagram illustrating a clinician programmer for use inthe system of FIG. 1.

FIG. 5 is a block diagram illustrating a quantitative sensory test unitfor use in the system of FIG. 1.

FIG. 6 is a flow diagram illustrating a technique for evaluating patientsensory response to rate neuromodulation efficacy.

FIG. 7 is a flow diagram illustrating another technique for evaluatingpatient sensory response to rate neuromodulation efficacy.

FIG. 8 is a flow diagram illustrating an additional technique forevaluating patient sensory response to rate neuromodulation efficacy.

FIG. 9 is a block diagram illustrating another system for evaluatingpatient sensory response to rate neuromodulation efficacy.

FIG. 10 is a flow diagram illustrating use of a visual analog scale(VAS) test as a threshold determination for analysis of sensoryresponse.

DETAILED DESCRIPTION

FIG. 1 is a block diagram illustrating a system 10 for evaluatingpatient sensory response to rate neuromodulation efficacy, such asefficacy of neurostimulation or drug delivery. As shown in FIG. 1,system 10 includes a neurostimulator 12, a programmer 14 and aquantitative sensory test (QST) unit 16. System 10 implements atechnique for rating neuromodulation efficacy based on evaluation of theresponse of the patient to external sensory stimuli, such as electrical,vibratory, tactile, thermal, pressure or chemical stimulation before andduring delivery of neurostimulation therapy.

External chemical sensory stimulation may involve delivery of a drug tothe patient to elicit a sensory response, e.g., capsaicin topicallyapplied to the skin to excite unmyelinated fibers or nitric oxide donorsto cause vasodilation, or to temporarily change the patient's painsymptoms, e.g., an intraspinal dose of clonidine or phentolamine tosuppress the sympathetic system, or an intraspinal dose of an NMDAblocker such as Ketamine.

System 10 delivers external sensory stimuli on a quantitative basis in acoordinated manner with delivery of neurostimulation therapy, andgenerates rating information for neuromodulation efficacy based onpatient sensory response to the stimuli. The efficacy rating may pertainnot only to the efficacy of neurostimulation but also drug delivery if asufficient correlation between efficacy of both types of neuromodulationhas been made. In operation, programmer 14 controls neurostimulator 12to delivery neurostimulation therapy to a patient, and controls QST unit16 to apply selected external sensory stimuli to the patient's body.Programmer 14 records the patient's report, including verbal orphysiological responses to the stimuli, as indicated by the clinician orthe patient.

System 10 may support delivery of different types of sensory stimuli,e.g., electrical and vibratory stimuli, and evaluation ofneuromodulation efficacy based on patient sensory response to thedifferent stimuli types. For example, the effect of neurostimulationtherapy on sensory perception thresholds, pain perception thresholds,pain tolerance limits and the like for different types of stimuli may bemeasured and evaluated to determine short-term efficacy ofneurostimulation, and possibly drug delivery.

Hence, even if the evaluation process makes use of electricalneurostimulation, the efficacy rating may also apply to drug delivery asanother form of neuromodulation. Drug delivery for neuromodulation mayinclude delivery of a drug to a patient orally, by injection, byimplantable drug pump, by external drug pump, by transdermal patch orother delivery mechanisms. Regardless of the type of sensory measurementperformed, system 10 is used to make a comparison of the applicablemeasurements, with and without application of neuromodulation. In thismanner, system 10 may be used to evaluate the effect of neuromodulationtherapy on patient response to some types of sensory stimuli, providingan indication of short-term (diagnostic) and long-term (prognostic)success of the neuromodulation therapy.

In each case, system 10 may consider patient sensory response tomultiple types of external sensory stimuli, and also patient subjectiveresponse to the neuromodulation therapy or its side effects, to providea correlation that promotes selectivity, sensitivity and specificity.Hence, the patient may provide reports in terms of subjective inputconcerning perceived efficacy, such as perceived pain relief andcoverage area, as will be described in greater detail below.

System 10 may be used in the clinic, or even at home by the patient insome embodiments, to test various parameters of neurostimulation,including polarities of electrodes, to determine which one best changesthe patient sensory response to the QST-based external sensorystimulation. If system 10 is used at home, QST stimulation activationand settings may be blinded to the patient, or they may be given to thepatient when the tests are done, for the patient to look up theinterpretation, and adjust the therapy.

Neurostimulator 12 may include an implanted or external pulse generatorand one or more implanted leads with electrodes to deliverneurostimulation energy to a patient. For external applications,neurostimulator 12 may be coupled to one or more implanted leads via apercutaneous lead extension for a trial of several days or weeks. Inother embodiments, neurostimulator 12 may be temporarily implantedwithin the patient and coupled to one or more implanted leads via animplanted lead extension. Neurostimulator 12 may be a trialneurostimulator, often called a screener, that is used to evaluatepossible implantation of a chronic neurostimulator in a patient.

A clinician contemplating implantation of a neurostimulation device ordrug delivery device to treat patients may consider the patient'shistory, symptoms, and prior therapies or therapy failures as a way topredict efficacy of neurostimulation therapies. In addition, theclinician may rely on trial neurostimulation. Trial neurostimulation mayinvolve placement of a trial lead to screen the patient at home for ashort period of time, such as a week, to determine if the therapy iseffective in relieving the symptoms.

When the patient returns to the clinic, he is asked about hisexperiences. In addition, the patient may use a patient report of painrelief such as a visual analog scale (VAS), report of percent painrelief, word choice lists, validated pain and activities questionnaires,or other techniques, to quantify and qualify the efficacy of thetreatment. In some embodiments, system 10 may make use of a combinationof tests and stimulation parameters, which the patient uses at homeduring the testing phase, and results from a particular trial may beused, automatically or with patient cooperation, to direct the nexttrial.

In accordance with the invention, the patient also undergoes QST-basedexternal sensory stimulation in the clinic to assess the effects of theneurostimulation therapy in altering patient sensory response. If thepatient's sensory response, alone or in combination with theneuromodulation efficacy observed during the trial, indicates likelihoodof successful therapy, a decision to replace neurostimulator 12 with achronic, implantable neurostimulator or drug delivery device can be madeby the clinician with heightened confidence.

In particular, the patient may have a placebo response, and these testscan be used to correlate changes in physiological responses to stimulidue to the therapy to the subjective feedback. With experience andresearch, the sensitivity and specificity of the algorithm used may beso great that it is more reliable than the patient's oral feedback, andthe medical profession may prefer to use it, or to extend a trial ifthere is a discrepancy between a patient's oral feedback and the sensorymeasurements.

Neurostimulator 12 delivers neurostimulation therapy to the patientaccording to one or more neurostimulation therapy programs. Aneurostimulation therapy program may include values for a number ofparameters, and the parameter values define the neurostimulation therapydelivered according to that program. In embodiments whereneurostimulator 12 delivers neurostimulation therapy in the form ofelectrical pulses, the parameters may include voltage- orcurrent-controlled pulse amplitudes, pulse widths, pulse rates, and thelike. In embodiments where drugs are delivered, parameters may includedosage and timing, or even the use of placebos.

Further, the parameters for a program may include informationidentifying which electrodes have been selected for delivery of pulsesaccording to the program, and the polarities of the selected electrodes.If the patient is being evaluated for an implantable drug deliverydevice, rather than an implantable neurostimulator, a single externalsensory test program or small set of programs found to be prognostic asto drug delivery efficacy may be selected. If the patient is beingevaluated for an implantable neurostimulator, however, evaluation ofdifferent programs may aid not only in determining whether to implant aneurostimulator, but also in identifying specific programs that may beefficacious.

For example, the trial neurostimulation period also may assist theclinician in selecting values for a number of programmable parameters inorder to define the neurostimulation therapy to be delivered to apatient. For example, the clinician may select an amplitude, which maybe current- or voltage-controlled, and pulse width for a stimulationwaveform to be delivered to the patient, as well as a rate or frequencyat which the pulses are to be delivered to the patient. In addition, theclinician also selects particular electrodes within an electrode setcarried by an implanted lead to be used to deliver the pulses, and thepolarities of the selected electrodes.

QST unit 16 may comprise any of a variety of devices capable of applyingsensory stimuli to the patient. For example, the stimuli may take theform of electrical stimulation, vibratory stimulation, thermalstimulation, tactile stimulation, or a combination of two or more of theforegoing types of stimulation. The sensory stimulation may be appliedwithout neurostimulation to obtain baseline sensory measurements, andthen with neurostimulation during the therapy trial in order to obtaintest measurements and identify changes that reveal the effect ofneurostimulation on the patient's sensory processes. In someembodiments, QST unit 16 may also deliver sensory stimulation bydelivery of a drug to the skin (external) or intraspinally (internal) tocause a change in the patient's pain symptoms, or to cause a controlleddegree of pain or affect the autonomic nervous system.

In an exemplary embodiment, QST unit 16 may generate both electrical andvibratory stimulation, although not necessarily at the same time.Consideration of the patient's recorded responses to multiple types ofsensory stimuli may provide a correlative relationship that promotesselectivity and specificity in evaluating neuromodulation therapy.Commercially available devices may be used, e.g., the NervScan™ LLCdevice of Neurotron, Inc., or the VSA-3000 Vibratory Sensory Analyzer ofMedoc, Inc., or even any of the commercially available TENS(transcutaneous electrical nerve stimulation) devices, which usecutaneous electrodes.

In some embodiments, programmer 14 serves as a platform to controloperation of both neurostimulator 12 and QST unit 16, e.g., in acoordinated manner. In addition, programmer 14 may provide features tosupport evaluation of a patient's responses to sensory stimuli appliedby QST unit 16, and thereby judge the efficacy of the neurostimulationtherapy applied by neurostimulator 12. In other embodiments,neurostimulator 12 and QST unit 16 may be controlled separately, e.g.,by a neurostimulation programmer in the case of neurostimulator 12 andby an integrated control unit in the case of QST unit 16. Alternatively,programmer 14 and QST unit 16 may be integrated with one another forclinician convenience, into the trial therapy screening device, or eveninto the fully implanted neurostimulation device. As will be described,in each case, system 10 provides features to carry out neurostimulation,application of external sensory stimulation, and recording andevaluation of patient sensory response.

A clinician may use programmer 14 to not only program trialneurostimulation therapy delivered by neurostimulator 12 for thepatient, but also select neurostimulation therapy programs for animplanted neurostimulator if implantation is elected following the trialperiod. In particular, the clinician may use programmer 14 to createneurostimulation therapy programs based on efficacy, including symptomrelief, coverage area relative to symptom area, and side effects, aswell as observed effects of the neurostimulation programs on patientsensory response to the QST stimuli. In particular, as will bedescribed, effects of the neurostimulation program in modifying patientsensory response to particular external sensory stimuli applied by QSTunit 16 may provide a reliable indication of short-term efficacy andlong-term neurostimulation success.

In another embodiment, during trial neurostimulation, components of thetherapy delivering device are not implanted in the patient, nor arethere percutaneous extensions. Rather, a TENS (transcutaneous electricalnerve stimulation) device is used as neurostimulator 12. The TENS unitmay produce therapeutic benefit on its own, and hence feel and performmuch like an implanted neurostimulation screening device. Alternatively,it may cause changes in processing of sensory information very similarto those of implanted neurostimulation devices, which can be fullyexplored using the QST unit 16.

FIG. 2 is a flow diagram illustrating a process for evaluating patientsensory response to rate neuromodulation efficacy, such as implantedneurostimulation device efficacy or implanted drug delivery deviceefficacy. As shown in FIG. 1, the process involves activating QST unit16 to deliver QST stimuli (18) such that external sensory stimulation isapplied to a patient. The external sensory stimulation may be applied ina series of controlled amplitude or frequency steps to obtain sensoryresponse information such as perception thresholds, pain thresholds,pain tolerance limits or other sensory information. Upon obtainingbaseline sensory response measurements from the patient (20), which maybe recorded by programmer 14, neurostimulator 12 activates delivery ofneurostimulation therapy to the patient (22). In conjunction withdelivery of neurostimulation by neurostimulator 12, QST unit 16 deliversQST stimuli to the patient (24).

Programmer 14 obtains patient neurostimulation sensory “test”measurements (26) in order to assess any change in sensory response ofthe patient to the QST stimuli during the application ofneurostimulation. The sensory measurements obtained during applicationof neurostimulation therapy will be referred to herein asneurostimulation sensory measurements or “test” measurements todistinguish those measurements from the baseline sensory measurementsobtained when neurostimulation therapy is not applied. Programmer 14compares the baseline and neurostimulation sensory test measurements(28), and then rates the efficacy of neuromodulation based on thecomparison (30).

The neuromodulation efficacy may be rated in terms of both short-termefficacy and likelihood of long-term success. A wide variety ofmeasurements may be made, and additional measurements may be derived, tocontribute to the efficacy rating, such as the patient's subjectivereports on the amount of pain relief, e.g., percent relief, visualanalog scale, or word choice, responses to lists of words describingtheir condition or satisfaction, responses recorded in validatedmeasurement instruments and questionnaires, e.g., Oswestry Inventory,SF-36 Inventory, or Sickness Impact Profile.

FIG. 3 is a conceptual diagram illustrating the system 10 of FIG. 1 ingreater detail. As shown in FIG. 3, neurostimulator 12 may include ahousing 31 with a connector block 32 to attach to a lead 34. Lead 34 isimplantable and includes a plurality of ring electrodes 36 disposedadjacent a distal tip of the lead. A lead extension 38 and coupler 40receive lead 34, and couple the lead to connector block 32 forconnection to pulse generator electronics within neurostimulator 12. Insome embodiments, housing 31 is designed for temporary implantationwithin the patient. In other embodiments, housing 31 may be external tothe patient. In this case, lead extension 38 may be a percutaneous leadextension.

Electrodes 36 are located proximate an appropriate stimulation site,e.g., along the spine for spinal cord stimulation (SCS) to reduce painexperienced by the patient. However, the invention is not limited to theconfiguration of leads 16 shown in FIG. 1 or the delivery of SCStherapy. For example, one or more leads 16 may extend fromneurostimulator 12 to the brain (not shown) of the patient, andneurostimulator 12 may deliver deep brain stimulation (DBS) therapy topatient to treat, for example, tremor or epilepsy. As further examples,one or more leads 16 may be implanted proximate to the pelvic nerves(not shown) or stomach (not shown), and neurostimulator 12 may deliverneurostimulation therapy to treat incontinence, gastroparesis, or sexualdysfunction. The form of the QST stimuli may vary in modality, or thesite of the application of the QST stimuli may vary appropriately foreach of these therapies.

In the example of FIG. 3, programmer 14 may take the form of a handheldor desktop computing device with a user interface such as a touchscreen42. Touchscreen 42 serves as a user interface to permit a clinician toview information presented by programmer 14, and enter information tocontrol application of neurostimulation therapy, including programmingof parameters within neurostimulator 12, e.g., via a wired or wirelessconnection 41. In some embodiments, programmer 14 may include a keypadand pointing device that permit a user to interact with the programmer.

In other embodiments, as depicted in FIG. 3, a touchscreen 42 permitsthe user to input information, e.g., using a stylus. Programmer 14 mayaccept information from the clinician to control application of externalsensory stimulation by QST unit 16, e.g., via a wired or wirelessconnection 43. Upon application of neurostimulation therapy and externalsensory stimulation, the clinician may enter information concerning thepatient's sensory responses and other efficacy-related information, viatouchscreen 42. Touchscreen 42 is depicted in FIG. 3 for purposes ofexample, and programmer 14 is in no way limited to a particular type ofuser interface.

With further reference to FIG. 3, QST unit 16 includes a display screen44 to present status information concerning external sensory stimulationapplied to a patient by the QST unit. The status information may becoded, especially as regards intensity of the applied stimulus. Also, inthe example of FIG. 3, QST unit 16 may include various input buttons46A-46C (hereinafter buttons 46), or other controls, to select differenttypes, levels or programs for delivery of external sensory stimulation.In addition, QST unit 16 may include input media, such as up/downbuttons, 48, 50, for increasing or decreasing stimulation levels, orstepping through different options. Other types of input media may beused, such as analog controls, touchscreens, switches, sliders, and thelike. As an alternative, or in addition, the functionality of buttons46, 48, 50 may be determined by similar input media presented byprogrammer 14.

In the example of FIG. 3, QST unit 16 is capable of delivering severalmodes of sensory stimuli. For example, QST unit 16 may apply electricalcurrent to a patient via electrodes 56A, 56B, which are coupled to theQST unit via leads 58A, 58B, respectively. Electrodes 56 may be surfaceelectrodes that can be adhesively attached to the skin at a desiredlocation on the patient's body. Current travels between electrodes 56 tostimulate the patient's tissue. Also, QST unit 16 may be coupled todrive a vibration generator 60 via a lead 62. Vibration generator 60 maybe configured to attach to or be placed upon a portion of the patient'sbody to deliver vibratory energy to the patient. In each case, QST unit16 controls parameters associated with delivery of the external sensorystimulation, such as level, frequency, duration and the like.

Electrodes 56 and vibration generator 60, or other sources of sensorystimulation, may be placed on the patient's skin at a position desiredby the clinician. In some cases, it may be desirable to place electrodes56 and vibration generator 60 in a region implicated by a particularsymptom. If the patient suffers from complex regional pain syndrome(CRPS), for example, it may be desirable to apply the external sensorystimulation in the region in which pain and other symptoms appear to befocused. In other cases, it may be desirable to apply the externalsensory stimulation at a point in or near a suspected propagation pathfrom the patient's nervous system to the region of pain.

It is anticipated that application of the sensory stimuli could beoptimally done in or along the same dermatome, thereby affecting thesame spinal cord segment as the pain and as the neurostimulation site.If the neurostimulator 12 used for trial neurostimulation is a TENSdevice, then its skin electrodes might be placed in the middle of theskin area of worst pain, and the sensory stimuli could be delivered tothe fingers or toes of that same dermatome. Alternatively, the externalsensory stimulation may be applied in locations that are not associatedwith a region of pain to prevent discomfort.

FIG. 4 is a block diagram illustrating a neurostimulation programmer foruse in the system of FIG. 1. As shown in FIG. 4, clinician programmer 14may include a processor 64, a user interface 66, a programming interface68, a QST interface 70, and a memory 72. Processor 64 executesinstructions stored in memory 72 to communicate with neurostimulator 12via programming interface 68 and QST unit 16 via QST interface 70. Inparticular, processor 64 programs neurostimulator 12 to use differentamplitudes, pulse widths, rates, and electrode configurations asspecified by different neurostimulation programs 74 stored in memory 72.Memory 72 may include any volatile, non-volatile, fixed, removable,magnetic, optical, or electrical media, such as a RAM, ROM, CD-ROM, harddisk, removable magnetic disk, memory cards or sticks, NVRAM, EEPROM,flash memory, and the like.

Processor 64 may select neurostimulation programs 74 based on a storeddevice configuration 76 that defines the configuration and capabilitiesof neurostimulator 12. Programming interface 68 may take the form of awired or wireless communication medium. Processor 64 drives QST unit 16via QST interface 70 to perform one or more QST programs 78 stored inmemory. Processor 64 may include a microprocessor, a controller, a DSP,an ASIC, an FPGA, discrete logic circuitry, or the like. QST programs 78may define different types of external sensory stimulation, differentprocesses for application of external sensory stimulation, andcombinations of different types of external sensory stimulation to beapplied to the patient. QST interface 70 may take the form of a wired orwireless communication medium. In some embodiments, however, clinicianprogrammer 14 may be integrated with QST unit 16 to form an integratedtrial neurostimulation and neuromodulation efficacy rating system.

Processor 64 further executes a rating engine 80 to accept informationfrom a user, e.g., via user interface 66, concerning the efficacy ofneurostimulation therapies and the responses of the patient to externalsensory stimulation both before and during application ofneurostimulation. For example, rating engine 80 may accept informationconcerning the parameters associated with a particular neurostimulationprogram, the types and amounts of external sensory stimulation appliedto a patient, and subjective responses of the patient.

Rating engine 80 may take into account baseline sensory measurements inthe absence of neuromodulation and sensory “test” measurements takenduring application of neuromodulation, and compare the measurements todetermine the effect of the neuromodulation therapy. Changes in sensoryor pain perception thresholds, pain tolerance limits and other changesmay be considered in evaluating the effect of neuromodulation therapy.Rating engine 80 may also use non-sensory information in determining itsoutput, such as patient selection of words from lists, patientinformation from past history, medications usage, patient evaluations oninventories (Oswestry, SF-36 and others) or even patient subjectivelyreported or explicitly recorded activity level.

FIG. 5 is a block diagram illustrating a quantitative sensory test unitfor use in the system of FIG. 1. As shown in FIG. 5, QST unit 16includes a processor 82, a programmer interface 84, user interface 86,an electrical generator 88, a vibration generator 90, and a memory 92.Memory 92 stores one or more QST programs 94 that define parametersassociated with delivery of external sensory stimulation, such as types,levels, and durations. Memory 92 may include any volatile, non-volatile,fixed, removable, magnetic, optical, or electrical media, such as a RAM,ROM, CD-ROM, hard disk, removable magnetic disk, memory cards or sticks,NVRAM, EEPROM, flash memory, and the like. Programmer interface 84communicates with QST interface 70 of clinician programmer 14. Userinterface 86 may correspond to display 44, and buttons 46, 48, 50 ofFIG. 3.

Processor 82 controls the electrical generator 88 by providingparameters associated with delivery of electrical stimulation currentbetween electrodes 56 via leads 58. Processor 82 may include amicroprocessor, a controller, a DSP, an ASIC, an FPGA, discrete logiccircuitry, or the like. Processor 82 also controls vibration generator90 by providing parameters associated with delivery of vibratory energyto the patient. The control of electrical generator 88 and vibrationgenerator 90 may follow parameters specified by QST programs 94.Although electrical and vibratory stimulation are depicted in FIG. 5 forpurposes of illustration, additional or alternative types of externalsensory stimulation may be provided by QST unit 16. However, delivery ofboth electrical and vibratory stimulation may yield aggregate patientsensory response data that is more specific and selective in indicatingthe likelihood of short-term and long-term success for an implantableneurostimulator.

In operation, processor 82 responds to input from a user or instructionscommunicated from clinician programmer 14 to selectively apply each typeof external sensory stimulation to the patient. To obtain baselinesensory measurements, QST unit 16 may apply electrical stimulation in aseries of steps with increasing amplitude or duration. In someembodiments, the electrical stimulation may be delivered as a sinusoidalwaveform or other waveform stimulation pulses at various frequencies,including frequencies in the range of 5 to 250 Hz, and possibly higher,and at various amplitudes, which may be successively increased tocapture a nonpainful perception threshold, followed by a pain perceptionthreshold and then a pain tolerance limit.

For electrical stimulation, the pain tolerance limit may represent themaximum stimulation that a patient can withstand in terms of pain level.For example, the patient or the clinician may record the first step atwhich the patient can actually perceive the stimulation, and then alsorecord the step at which the stimulation reaches the patient's paintolerance ability. If the patient's sensory response changes withneurostimulation such that the patient can tolerate more QST pain, theremay be a helpful correlation to the efficacy of neuromodulation inrelieving pain symptoms suffered by the patient.

For vibratory stimulation, the perception threshold may represent thethreshold for sensation of vibratory stimuli, without measuring apainful sensory response. This type of vibratory stimulation test couldbe performed several times during the course of trial neurostimulationin order to assess any changes. The vibratory stimulation may beaccomplished with a voicecoil, piezoelectric, or other type ofelectromechanical transducer capable of generating vibration at selectedfrequencies and amplitudes. Again, patient sensory response to vibratorystimulation may be characterized in terms of perception thresholds, andpossibly pain thresholds at higher amplitudes, e.g., a patient hasdynamic mechanical allodynia. The perception threshold for vibration orlight touch is usually a function of nerve fibers that have a largediameter (called A-beta fibers); while perception of pain is usually afunction of nerve fibers with smaller diameters (A-delta, or C).

Other types of stimulation may include tactile stimulation in which apatient may be asked to resolve the presence of two or more tactilepoint sources based on varying distances between the point sources andvarying contact force. Patient sensory response to tactile stimulationmay be characterized in terms of the patient's ability to discriminatedifferent tactile point sources, given a particular separation distanceand contact force. Thermal stimulation may involve delivery of heat tothe patient, i.e., thermal pulse trains or steady heat ramps. Forthermal stimulation, patient sensory response can be characterized interms of perception thresholds indicating the patient's first conscioussensation of heat or cold, and pain thresholds for first sensations thatare described as painful heat or cold by the patient, and pain tolerancelimits as the hottest or coldest pain that the patient could tolerate.

The patient may also give a subjective verbal report of the pain levelwith any particular thermal stimulus, by giving an oral analog scale,i.e., saying that on a scale of 0 (no pain) to 100 (worst possiblepain), the pain at that instance was, e.g., “65.” This sensory responseinformation may be entered into QST unit 16 or clinician programmer 14.Similar baseline measurement information can be obtained for vibratorystimulation, as well as for other types of stimulation, if desired. Ineach case, the baseline measurements are obtained in the absence ofneurostimulation. The measurements may be obtained in one session,different sessions, or over a series of sessions. For example, themeasurements may be taken on a daily basis throughout the patient'susage of the trial neurostimulation therapy, or even with each time thepatient changes the therapy in his own home.

Once the baseline measurements are obtained, the clinician activatesneurostimulator 12 via clinician programmer 14 to apply neurostimulationtherapy and thereby obtain test measurements in the presence of bothneurostimulation and sensory stimulation. In particular, in addition torecording basic efficacy information, e.g., noting pain relief or othertherapeutic effect as well as perceptible side effects, as subjectivelyobserved by the patient, clinician programmer 14 may be used to recordsensory measurements. Specifically, for each neurostimulation programapplied to the patient, clinician programmer 14 or the clinician alsomay apply external sensory stimulation using QST unit 16. In thismanner, the clinician can evaluate the effect of neurostimulation onpatient sensory response to the external sensory stimulation.

Comparison of the baseline response measurements to the neurostimulationsensory test measurements may provide a reliable indication ofshort-term efficacy and long-term success of neurostimulation therapy.This indication can help the clinician make a more confident decision ofwhether to implant a neurostimulation device. In addition, the resultingcomparison information can be formulated for different neurostimulationprograms and analyzed by the rating engine implemented by clinicianprogrammer 14 to identify the most effective neurostimulation programs.This can allow the clinician's staff or the patient to try numerousneurostimulation parameters, and rate the efficacy for each one, in amanner less subjective than current techniques.

FIG. 6 is a flow diagram illustrating a technique for evaluating patientsensory response to rate neuromodulation efficacy. The technique may beimplemented by system 10 of FIG. 1. As shown in FIG. 6, upon activatingthe QST stimuli (96), baseline sensory measurements are obtained fromthe patient and recorded (98). Again, the external sensory stimulationmay take a variety of forms, including electrical stimulation, vibratorystimulation, thermal stimulation, tactile stimulation or a succession ofdifferent stimulation types. The baseline sensory measurements mayinclude perception thresholds, tolerance limits or other measurements.

To evaluate the change in patient sensory response caused byneurostimulation, a selected neurostimulation program is activated(100), e.g., by clinician programmer 14. The, the QST stimuli are thenactivated (102), and neurostimulation sensory test measurements areobtained (104) in the presence of sensory stimulation andneurostimulation, and recorded. Upon comparison of the baseline andneurostimulation sensory test measurements (106), clinician programmer14 determines whether the comparison is favorable to neurostimulatorimplantation.

In particular, if the sensory measurements change favorably uponapplication of a neurostimulation program, the program may be identifiedas potentially efficacious. For example, if the comparisons arefavorable (110), the program is flagged (112). The comparison may simplybe an indication of whether a perception threshold is increased ordecreased relative to the baseline perception threshold. Similarly, therating may reflect whether the patient can tolerate more or less pain orother stimulation. An increased sensory perception or sensory tolerancelimit may be viewed as favorable. Even if a program is flagged based ona favorable QST result, it should be evaluated for clinical result,e.g., actual relief of symptoms.

In particular, if a patient's perception threshold or stimulationtolerance limit is increased during application of neurostimulation, theeffect of the neurostimulation program on the sensory response of thepatient may be diagnostic of short-term neurostimulation success andprognostic of long-term success. Multiple neurostimulation programs maybe evaluated for their effect on the patient sensory response, andflagged if they have a favorable effect. Once the end of the programs isreached (114), the process stops (116). If the end of the programs hasnot been reached, the process repeats by selecting the nextneurostimulation program (118). The results can be stored in clinicianprogrammer 14 to aid a clinician in not only determining whetherimplantation is advisable, but also selecting a particularneurostimulation program once implantation is done

FIG. 7 is a flow diagram illustrating another technique for evaluatingpatient sensory response to rate neuromodulation efficacy. The techniqueof FIG. 7 corresponds generally to the technique of FIG. 6, but involvesthe analysis of sensory response for two different types of externalsensory stimulation. For example, the effects of neurostimulation onpatient sensory response to electrical stimulation and vibratorystimulation may provide a more specific and selective indication of thelikely efficacy of neuromodulation. Rather than focusing on only asingle type of external sensory stimulation, a requirement thatneurostimulation have a favorable effect on sensory response for two ormore different types of stimulation provides a correlative relationshipthat increases the confidence of the decision to implant aneurostimulator. In the example of FIG. 7, electrical and vibratorystimulation are illustrated as two types of stimulation.

In some embodiments, a second type of stimulation may be applied only inthe event favorable results are not obtained with the first type ofstimulation by a sufficiently wide margin. For example, ifneurostimulation causes a substantial favorable change in patientsensory response to external electrical stimulation, a prediction may bemade that the neurostimulation is likely to be efficacious, therebywarranting implantation. If the neurostimulation causes a smallerchange, e.g., below a predetermined threshold difference, then theclinician may elect to further investigate the effects of theneurostimulation on a second type of external sensory stimulation, suchas vibratory stimulation. If the neurostimulation causes a substantialchange in patient sensory response to the second type of stimulation,e.g., vibratory stimulation, a prediction of efficacy may be made withgreater confidence. In this case, measurement of changes in patientsensory responses to two different types of external sensory stimulationin the presence of neurostimulation may provide greater selectivity andspecificity in the prediction.

As shown in FIG. 7, baseline vibration measurements are obtained (120)during application of vibratory stimulation to the patient and in theabsence of neurostimulation. The baseline vibration measurements mayinclude a perception threshold. Then, baseline electrical measurementsmay be obtained (122). The baseline electrical measurements may includea perception threshold and a pain tolerance limit. Upon activation of aneurostimulation program, test measurements are obtained for thevibration and electrical stimulation (126, 128). Upon comparison of thebaseline and neurostimulation test vibration and electrical measurements(130, 132), if both comparisons are favorable, the neurostimulationprogram under study is flagged (138). If the end of programs has beenreached (140), the process stops (142). Alternatively, the next programis selected (144).

According to another embodiment, baseline vibration measurements areobtained during application of vibratory stimulation to the patient.Then, baseline electrical measurements may be obtained. Upon activationof a neurostimulation program, similar test measurements are obtainedfor the vibration, and the baseline and neurostimulation vibration testmeasurements are compared. If the comparison is favorable, thenelectrical measurements may be taken for patient sensory response toexternal electrical stimulation. If the vibratory comparison is notfavorable, however, the clinician or patient may simply forego theelectrical measurement and conclude that the applicable neurostimulationprogram is not likely to be efficacious. As a variation, the process maytake the baseline electrical measurement and neurostimulationmeasurement only if the vibratory measurements are not favorable. Inanother embodiment, if a patient's visual analog score (VAS) score riseswith neurostimulation, then the process can be terminated withouttesting other measurements such as electrical or vibratory externalsensory stimulation.

FIG. 8 is a flow diagram illustrating an additional technique, asdescribed above, for evaluating patient sensory response to rateneuromodulation efficacy. As shown in FIG. 8, the technique involvesobtaining baseline vibration sensory measurements (patient response tovibratory stimulation) (144), activating a selected neurostimulationprogram (146), obtaining vibration sensory test measurements duringneurostimulation (148), and comparing the baseline and neurostimulationvibration sensory test measurements (150). If the comparison isfavorable and definitive (152), i.e., neurostimulation changes thepatient sensory response favorably by a sufficiently wide margin, theprogram is flagged (154) as being potentially efficacious. If thecomparison is not favorable, the next program is selected for evaluation(166, 170) unless all programs of interest have been investigated (168).

If the comparison is favorable but not definitive, electricalmeasurements are taken. Specifically, the technique then involvesobtaining baseline electrical sensory measurements (patient response toexternal electrical stimulation), i.e., in the absence ofneuromodulation therapy (156), activating neurostimulation (158), andobtaining neurostimulation electrical test measurements (160), andcomparing the baseline and neurostimulation electrical test measurement(162). If the comparison is favorable, the program is flagged (154). Ifthe program is favorable but not definitive, or unfavorable, the nextprogram is selected (166, 170). The process stops (168) when the end ofthe programs is reached (166). Although the first and second types ofstimulation described with respect to FIG. 8 are vibratory andelectrical stimulation, electrical could be tried first rather thanvibratory, and other types of stimulation could possibly be used inplace of electrical or vibratory stimulation.

Application of external sensory stimulation in the form of electrical,vibratory, tactile, thermal, and chemical stimulation have beendescribed herein for purposes of illustration. In addition, a number ofmeasurements, such as perception thresholds and tolerance limits, havebeen described. Changes in patient sensory response to electrical andvibratory stimulation may correlate particularly well to short-term andlong-term efficacy of neurostimulation therapy such as spinal cordstimulation (SCS) for pain relief. However, a system as described hereinmay be configured to apply other types of stimulation, and obtain andanalyze a variety of different measurements indicative of patent sensoryresponse. Further examples of external sensory types and appropriatepatient sensory response measurements will now be described in furtherdetail.

A system as described herein may be adapted to make use of the differentstimulation types and measurements to predict short-term and long-termefficacy of an implantable neurostimulator for a given patient. Examplesof different types of external sensory stimulation and possible patientsensory response measurements are described below. For electricalstimulation, vibratory stimulation, or thermal stimulation, measurementsmay include nonpainful perception thresholds, pain perceptionthresholds, and pain tolerance limits.

Alternative measurements may be obtained in the form of pain ratings,e.g., where the patient ranks pain caused by a given level of electricalor thermal stimulation on a numerical scale, or where the patient uses avisual analog scale (VAS). The patient also may use word rankings ofpain such as no pain, modest pain, mild pain, noticeable pain, severepain, and the like. Other possible rating scales, serving as painmeasurement vehicles, include reference to the McGill pain rating scale,activities of daily living metrics, reference to established paininventories such as the Oswestry, SF-36, or Minnesota MultiphasicPersonality Inventory (MMPI) indices. For tactile stimulation, tactilemeasurements may include perception thresholds such as pin prick orcotton wisp sensations, and discrimination of multiple tactile pointsources. These tests may use other QST devices, such as von Freyfilaments. In each case, regardless of the precise type of stimulationand type of measurement, a correlation may be discovered between achange in the measurement due to neurostimulation and the likelyshort-term or long-term efficacy of neuromodulation. In each case, arating engine may be designed to rate efficacy based on the resultingpatient report information.

For another possible test, it might not be necessary to implant a trialSCS lead. It may be possible to provide TENS at a site, and also performall the sensory tests at other sites, but probably in the samedermatome. This may be especially good as a trial for angina. TENS workswell for angina, usually. Spinal cord stimulation (SCS) may also work.In some applications, patients can be selected for SCS for angina (andimplant without screening) if TENS is performed (and it helps theangina) and the sensory tests are also changed.

FIG. 9 is a block diagram illustrating another system for evaluatingpatient sensory response to rate neuromodulation efficacy. The systemincludes a programmer 14 and a QST unit 16, as in the example of FIG. 1.As shown in FIG. 9, however, instead of an implantable trialneurostimulator, the system makes use of a TENS unit 170 to deliver thecutaneous neurostimulation used in evaluating changes in patient sensoryresponse to external sensor stimulation delivered by QST unit 16. TENSunit 170 may be advantageous because it does not require surgicalimplantation to be performed as part of the screening process; rather,the TENS unit 170 includes electrodes that are affixed to the surface ofthe patient's skin.

FIG. 10 is a flow diagram illustrating use of a visual analog scale(VAS) test as a threshold determination for analysis of sensoryresponse. As shown in FIG. 10, before deciding whether to evaluatechanges in patient sensory response, neurostimulation is applied to thepatient to obtain a comparison of VAS scores, before and duringneurostimulation. If the VAS score actually rises duringneurostimulation, it is unlikely that neuromodulation will beefficacious.

Accordingly, the various patient sensory response tests described hereincan simply be avoided if the VAS score rises with neurostimulation. Asshown in FIG. 10, this process involves obtaining a baseline VAS score(172), applying neurostimulation (174), obtaining a VAS score duringneurostimulation (176), and determining whether the VAS score roseduring neurostimulation (178). If so, the test is stopped (182). If theVAS score improved, however, the QST test or tests can be completed(180) to evaluate possible neuromodulation efficacy.

EXAMPLE

A pilot study was conducted using both a pain tolerance test (PTT) testand a vibrational threshold test at four hospitals. The equipment usedwas the NervScan™ LLC device, commercially available from Neurotron,Inc., of Baltimore, Md., USA, for PTT, and the TSA II NeuroSensoryAnalyzer, commercially available from Medoc Advanced Medical Systems, ofChapel Hill, N.C., USA, for vibration threshold measurements. Testingsites were the fingers and toes of three limbs, using the samedermatomes as the sites of the worst chronic neuropathic pain, and testswere done at baseline and after one week of trial SCS, with stimulationon. Patients had chronic radicular neuropathy or complex regional painsyndrome. Out of 10 patients with PTT data, 4 out of 5 patients whoachieved clinical success, i.e., had a complete SCS system implanted,had their PTT amplitude increase with SCS, versus only 2 of 5 who didnot see sufficient pain relief to have a complete SCS system implanted.

Out of 10 patients with vibration threshold measurements at baseline andafter a week of trial SCS, all six of six patients who achieved clinicalsuccess had their vibration threshold amplitude rise with SCS, versusonly two of four patients who had clinical failure at SCS trial. Thesewere trends only, and not statistically significant. However, it wasdiscovered that if one criteria is added to using these tests, theresults can be improved. If the test is not applied in cases wherepatients report that their pain actually increased with trial SCS(measured by VAS), then the specificity of the test improves for thosenot achieving clinical success, and thus not getting an internalized,fully-implanted, system. Thus, the combination of two QST tests and aclinical trial outcome report (VAS, subjective, from patient), may allowthe test to have improved sensitivity and specificity. In the abovecases, by excluding those patients with pain rising from SCS, thesensitivity becomes 80% for PTT and 100% for vibration threshold; andthe specificity is 100% for both tests.

Certain aspects of the invention may be embodied as a computer-readablemedium comprising instructions for causing a programmable processor tocarry out procedures in support of the techniques described herein. Forexample, software, firmware and/or hardware may be provided tofacilitate application of external sensory stimulation andneuromodulation, reporting of sensory response, and rating of efficacy.

Various embodiments of the invention have been described. However, oneskilled in the art will appreciate that various additions andmodifications can be made to these embodiments without departing fromthe scope of the invention. These and other embodiments are within thescope of the following claims.

1. A method comprising: applying a first type of external sensorystimulation to a patient; obtaining a baseline measurement of patientsensory response to the first type of external sensory stimulation;applying a second type of external sensory stimulation to a patient;obtaining a baseline measurement of patient sensory response to thesecond type of external sensory stimulation; applying neuromodulationtherapy to the patient simultaneously with application of the first typeof external sensory stimulation; obtaining a test measurement of patientsensory response to the first type of external sensory stimulationduring simultaneous application of the first type of external sensorystimulation and the neuromodulation therapy; applying neuromodulationtherapy to the patient simultaneously with application of the secondtype of external sensory stimulation; obtaining a test measurement ofpatient sensory response to the second type of external sensorystimulation during simultaneous application of the second type ofexternal sensory stimulation and the neuromodulation therapy; evaluatingefficacy of the neuromodulation therapy based on a comparison of thebaseline measurements and the test measurements.
 2. The method of claim1, wherein evaluating efficacy includes at least one of evaluatingdiagnostic efficacy and prognostic efficacy.
 3. The method of claim 1,wherein applying neuromodulation therapy includes at least one ofapplying neurostimulation therapy and drug delivery therapy.
 4. Themethod of claim 3, wherein the drug delivery therapy includes at leastone of delivery of a drug orally, by injection, by implantable drugpump, by external drug pump, and by transdermal patch.
 5. The method ofclaim 1, wherein applying neuromodulation therapy includes applyingneurostimulation therapy via one or more implanted neurostimulationleads.
 6. The method of claim 1, wherein applying neuromodulationtherapy includes applying neurostimulation therapy by transcutaneouselectrical nerve stimulation.
 7. The method of claim 1, wherein theexternal sensory stimulation includes at least one of tactile,vibrational, thermal, pressure, electrical, and chemical stimulation. 8.The method of claim 1, wherein the patient sensory response includes atleast one of a perception threshold, a pain threshold, and a tolerancelimit.
 9. The method of claim 1, wherein the patient sensory responseincludes a patient report relating to perceived pain relief.
 10. Themethod of claim 8, wherein the patient report includes input indicatedin a visual analog scale format.
 11. The method of claim 1, furthercomprising performing the method in one of a clinic and a patient home.12. The method of claim 1, further comprising using an integrated deviceto apply at least one of the first and second types of external sensorystimulation and to control the application of the neurostimulationtherapy.
 13. The method of claim 1, further comprising using a device tocontrol both a quantitative sensory testing device to apply at least oneof the first and second types of external sensory stimulation and aneuromodulation device to apply the neuromodulation therapy.
 14. Themethod of claim 1, wherein one of the first and second types of externalsensory stimulation includes electrical stimulation.
 15. The method ofclaim 1, wherein one of the first and second types of external sensorystimulation includes vibratory stimulation.
 16. The method of claim 1,wherein the first type of external sensory stimulation includesvibratory stimulation, and the second type of external sensorystimulation includes electrical stimulation.
 17. The method of claim 1,wherein applying neuromodulation therapy includes applying differentneurostimulation programs, the method further comprising obtainingmultiple test measurements of patient sensory response to the first andsecond types of external sensory stimulation during application of thedifferent neurostimulation programs, and identifying favorableneurostimulation programs based on the comparison of the baselinemeasurements and the test measurements for the first and second types ofexternal sensory stimulation.
 18. The method of claim 1, furthercomprising repeating the measurements following implant of animplantable neurostimulator in the patient.
 19. The method of claim 1,wherein the external sensory stimulation includes application of a drugto the patient.
 20. The method of claim 18, wherein the application of adrug includes at least one of topical application and intraspinalapplication of the drug.
 21. A system comprising: a first sensorystimulation unit to apply a first type of external sensory stimulationto a patient; a second sensory stimulation unit to apply a second typeof external sensory stimulation to the patient; a neuromodulation unitto apply neuromodulation therapy to the patient; a device to obtain abaseline measurement of patient sensory response to the first type ofexternal sensory stimulation without application of the neuromodulationtherapy, obtain a baseline measurement of patient sensory response tothe second type of external sensory stimulation without application ofthe neuromodulation therapy, obtain a test measurement of patientsensory response to simultaneous application of the first type ofexternal sensory stimulation and the neuromodulation therapy, obtain atest measurement of patient sensory response to simultaneous applicationof the second type of external sensory stimulation and theneuromodulation therapy, and evaluate efficacy of the neuromodulationtherapy based on a comparison of the baseline measurements and the testmeasurements.
 22. The system of claim 21, wherein the first and secondstimulation units are integrated within a common stimulation unit. 23.The system of claim 21, wherein the device evaluates at least one ofdiagnostic efficacy and prognostic efficacy.
 24. The system of claim 21,wherein the neuromodulation therapy includes at least one ofneurostimulation therapy and drug delivery therapy.
 25. The system ofclaim 24, wherein the drug delivery therapy includes one of delivery ofa drug by injection, by implantable drug pump, by external drug pump,and by transdermal patch.
 26. The system of claim 21, wherein theneuromodulation unit includes an implantable neurostimulation unit. 27.The system of claim 21, wherein the neuromodulation unit includes atranscutaneous electrical nerve stimulation unit.
 28. The system ofclaim 21, wherein the device includes a programmer that controls theneuromodulation unit.
 29. The system of claim
 28. wherein the programmeralso controls the sensory stimulation unit.
 30. The system of claim 21,wherein the external sensory stimulation includes at least one oftactile, vibrational, thermal, pressure, electrical, and chemicalstimulation.
 31. The system of claim 21, wherein one of the first andsecond types of external sensory stimulation includes electricalstimulation.
 32. The system of claim 21, wherein one of the first andsecond types of external sensory stimulation includes vibratorystimulation.
 33. The system of claim 21, wherein the first type ofexternal sensory stimulation includes vibratory stimulation and thesecond type of external sensory stimulation includes electricalstimulation.
 34. The system of claim 21, wherein the patient sensoryresponse includes at least one of a perception threshold, a painthreshold, and a tolerance limit.
 35. The system of claim 21, whereinthe patient sensory response includes a patient report relating toperceived pain relief.
 36. The system of claim 35, wherein the patientreport includes input indicated in a visual analog scale format.
 37. Thesystem of claim 21, wherein the neuromodulation unit applies differentneurostimulation programs, and the device obtains multiple testmeasurements of patient sensory response to the first and second typesof external sensory stimulation during application of the differentneurostimulation programs, and identifies favorable neurostimulationprograms based on the comparison of the baseline measurements and thetest measurements for the first and second types of external sensorystimulation.
 38. The system of claim 21, wherein the external sensorystimulation includes application of a drug to the patient.
 39. Thesystem of claim 38, wherein the application of a drug includes at leastone of topical application and intraspinal application of the drug. 40.A method comprising: applying external sensory stimulation to a patient,wherein the external sensory stimulation includes at least one oftactile, vibrational, thermal, pressure, chemical stimulation; obtaininga baseline measurement of patient sensory response to the externalsensory stimulation; applying neuromodulation therapy to the patientsimultaneously with application of the external sensory stimulation;obtaining a test measurement of patient sensory response to the externalsensory stimulation during simultaneous application of the externalsensory stimulation and the neuromodulation therapy; and evaluatingefficacy of the neuromodulation therapy based on a comparison of thebaseline measurements and the test measurements.
 41. The method of claim40, wherein evaluating efficacy includes at least one of evaluatingdiagnostic efficacy and prognostic efficacy.
 42. The method of claim 40,wherein applying neuromodulation therapy includes at least one ofapplying neurostimulation therapy and drug delivery therapy.
 43. Themethod of claim 42, wherein the drug delivery therapy includes at leastone of delivery of a drug orally, by injection, by implantable drugpump, by external drug pump, and by transdermal patch.
 44. The method ofclaim 40, wherein applying neuromodulation therapy includes applyingneurostimulation therapy.
 45. The method of claim 40, wherein thepatient sensory response includes at least one of a perceptionthreshold, a pain threshold, and a tolerance limit.
 46. The method ofclaim 40, wherein the patient sensory response includes a patient reportrelating to perceived pain relief.
 47. The method of claim 46, whereinthe patient report includes input indicated in a visual analog scaleformat.
 48. The method of claim 40, wherein applying neuromodulationtherapy includes applying different neurostimulation programs, themethod further comprising obtaining multiple test measurements ofpatient sensory response to the external sensory stimulation duringapplication of the different neurostimulation programs, and identifyingfavorable neurostimulation programs based on the comparison of thebaseline measurements and the test measurements for the external sensorystimulation.
 49. The method of claim 48, wherein the external sensorystimulation includes application of a drug to the patient.
 50. Themethod of claim 49, wherein the application of a drug includes at leastone of topical application and intraspinal application of the drug. 51.A system comprising: a sensory stimulation unit to apply externalsensory stimulation to a patient, wherein the external sensorystimulation includes at least one of tactile, vibrational, thermal,pressure, chemical stimulation; a neuromodulation unit to applyneuromodulation therapy to the patient; a device to obtain a baselinemeasurement of patient sensory response to the external sensorystimulation without application of the neuromodulation therapy, obtain atest measurement of patient sensory response to simultaneous applicationof the external sensory stimulation and the neuromodulation therapy, andevaluate efficacy of the neuromodulation therapy based on a comparisonof the baseline measurements and the test measurements.
 52. The systemof claim 51, wherein the device evaluates at least one of diagnosticefficacy and prognostic efficacy.
 53. The system of claim 51, whereinthe neuromodulation therapy includes at least one of neurostimulationtherapy and drug delivery therapy.
 54. The system of claim 53, whereinthe drug delivery therapy includes one of delivery of a drug byinjection, by implantable drug pump, by external drug pump, and bytransdermal patch.
 55. The system of claim 51, wherein theneuromodulation unit includes a neurostimulation unit.
 56. The system ofclaim 51, wherein the device includes a programmer that controls theneuromodulation unit and the sensory stimulation unit.
 57. The system ofclaim 51, wherein the patient sensory response includes at least one ofa perception threshold, a pain threshold, and a tolerance limit.
 58. Thesystem of claim 51, wherein the patient sensory response includes apatient report relating to perceived pain relief.
 59. The system ofclaim 58, wherein the patient report includes input indicated in avisual analog scale format.
 60. The system of claim 51, wherein theneuromodulation unit applies different neurostimulation programs, andthe device obtains multiple test measurements of patient sensoryresponse to the first and second types of external sensory stimulationduring application of the different neurostimulation programs, andidentifies favorable neurostimulation programs based on the comparisonof the baseline measurements and the test measurements for the first andsecond types of external sensory stimulation.
 61. The system of claim51, wherein the external sensory stimulation includes application of adrug to the patient.
 62. The system of claim 61, wherein the applicationof a drug includes at least one of topical application and intraspinalapplication of the drug.
 63. A method comprising: applying a first typeof external sensory stimulation to a patient; obtaining a baselinemeasurement of patient sensory response to the first type of externalsensory stimulation; applying a second type of external sensorystimulation to a patient; obtaining a baseline measurement of patientsensory response to the second type of external sensory stimulation;applying neuromodulation therapy to the patient simultaneously withapplication of the first type of external sensory stimulation; obtaininga test measurement of patient sensory response to the first type ofexternal sensory stimulation during simultaneous application of thefirst type of external sensory stimulation and the neuromodulationtherapy; evaluating efficacy of the neuromodulation therapy based on acomparison of the baseline measurements and the test measurements forthe first type of external sensory stimulation; if the evaluationindicates efficacy, applying neuromodulation therapy to the patientsimultaneously with application of the second type of external sensorystimulation; obtaining a test measurement of patient sensory response tothe second type of external sensory stimulation during simultaneousapplication of the second type of external sensory stimulation and theneuromodulation therapy; and evaluating efficacy of the neuromodulationtherapy based on a comparison of the baseline measurements and the testmeasurements for the first and second types of external sensorystimulation.
 64. A system comprising: a first sensory stimulation unitto apply a first type of external sensory stimulation to a patient; asecond sensory stimulation unit to apply a second type of externalsensory stimulation to the patient; a neuromodulation unit to applyneuromodulation therapy to the patient; a device to obtain a baselinemeasurement of patient sensory response to the first type of externalsensory stimulation without application of the neuromodulation therapy,obtain a baseline measurement of patient sensory response to the secondtype of external sensory stimulation without application of theneuromodulation therapy, obtain a test measurement of patient sensoryresponse to simultaneous application of the first type of externalsensory stimulation and the neuromodulation therapy, evaluate efficacyof the neuromodulation therapy based on a comparison of the baselinemeasurements and the test measurements, wherein device, if theevaluation indicates efficacy, obtains a test measurement of patientsensory response to simultaneous application of the second type ofexternal sensory stimulation and the neuromodulation therapy, andevaluating efficacy of the neuromodulation therapy based on a comparisonof the baseline measurements and the test measurements for the first andsecond types of external sensory stimulation.
 65. A method comprising:applying external sensory stimulation to a patient, wherein the externalsensory stimulation includes at least one of tactile, vibrational,thermal, pressure, and chemical stimulation; obtaining a baselinemeasurement of patient sensory response to the external sensorystimulation; applying neuromodulation therapy to the patientsimultaneously with application of the external sensory stimulation;obtaining a test measurement of patient sensory response to the externalsensory stimulation during simultaneous application of the externalsensory stimulation and the neuromodulation therapy; and evaluatingefficacy of the neuromodulation therapy based on a comparison of thebaseline measurements, the test measurements, and a patient report ofpain relief.
 66. The method of claim 65, wherein the patient report ofpain relief includes at least one of a report of percentage of painrelief, a visual analog scale (VAS) score, and a word choice.
 67. Asystem comprising: a sensory stimulation unit to apply external sensorystimulation to a patient, wherein the external sensory stimulationincludes at least one of tactile, vibrational, thermal, pressure, andchemical stimulation; a neuromodulation unit to apply neuromodulationtherapy to the patient simultaneously with application of the externalsensory stimulation; and a device to obtain a baseline measurement ofpatient sensory response to the external sensory stimulation, obtain atest measurement of patient sensory response to the external sensorystimulation during simultaneous application of the external sensorystimulation and the neuromodulation therapy, and evaluate efficacy ofthe neuromodulation therapy based on a comparison of the baselinemeasurements, the test measurements, and a patient report of painrelief.
 68. The method of claim 67, wherein the patient report of painrelief includes at least one of a report of percentage of pain relief, avisual analog scale (VAS) score, and a word choice.
 69. A methodcomprising: applying external sensory stimulation to a patient, whereinthe external sensory stimulation includes at least one of tactile,vibrational, thermal, pressure, electrical, and chemical stimulation;obtaining a baseline measurement of patient sensory response to theexternal sensory stimulation; applying neuromodulation therapy to thepatient simultaneously with application of the external sensorystimulation; obtaining a test measurement of patient sensory response tothe external sensory stimulation during simultaneous application of theexternal sensory stimulation and the neuromodulation therapy; andevaluating efficacy of the neuromodulation therapy based on a comparisonof the baseline measurements, the test measurements, and a visual analogscale (VAS) score.
 70. A system comprising: a sensory stimulation unitto apply external sensory stimulation to a patient, wherein the externalsensory stimulation includes at least one of tactile, vibrational,thermal, pressure, electrical, and chemical stimulation; aneuromodulation unit to apply neuromodulation therapy to the patientsimultaneously with application of the external sensory stimulation; anda device to obtain a baseline measurement of patient sensory response tothe external sensory stimulation, obtain a test measurement of patientsensory response to the external sensory stimulation during simultaneousapplication of the external sensory stimulation and the neuromodulationtherapy, and evaluate efficacy of the neuromodulation therapy based on acomparison of the baseline measurements, the test measurements, and avisual analog scale (VAS) score.